HSP110s exchange ATP for ADP on HSP70s:ADP

Stable Identifier
R-HSA-5252079
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

The substrate binding ability of heat-shock 70kDa proteins (HSP70s) is dependant on their bound state to either ATP or ADP. Release of a protein substrate is induced when HSP70s are bound to ATP and conversely, proteins substrates bind when HSP70s are bound to ADP. Intrinsic ATPase of HSP70s slowly hydrolyses ATP to ADP. This process can be speeded up by cochaperones such as HSP40s which stimulate ATPase activity. Nucleotide exchange factors (NEFs) regulate the lifespan of the HSP70:ADP:substrate complex by exchanging ADP for ATP, thus inducing the release of the substrate. Eukaryote NEFs include heat-shock protein 105kDa (HSPH1 aka HSP110) (Schuermann et al. 2008) and the BAG family molecular chaperone regulator (BAG) family (BAG1-5). BAGs inhibit the chaperone activity of HSP70s by promoting substrate release (Takayama et al. 1997, Takayama et al. 1999). HSC70-interacting protein (ST13 aka HIP) is a 48kDa tetrameric protein able to bind the ATPase domain of HSP70s and thought to stabilise the ADP state of HSP70s (Hohfeld et al. 1995, Prapapanich et al. 1996).

Literature References
PubMed ID Title Journal Year
8721986 Molecular cloning of human p48, a transient component of progesterone receptor complexes and an Hsp70-binding protein

Prapapanich, V, Chen, S, Nair, SC, Rimerman, RA, Smith, DF

Mol. Endocrinol. 1996
9305631 BAG-1 modulates the chaperone activity of Hsp70/Hsc70

Takayama, S, Bimston, DN, Matsuzawa, S, Freeman, BC, Aime-Sempe, C, Xie, Z, Morimoto, RI, Reed, JC

EMBO J. 1997
9873016 An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators

Takayama, S, Xie, Z, Reed, JC

J. Biol. Chem. 1999
7585962 Hip, a novel cochaperone involved in the eukaryotic Hsc70/Hsp40 reaction cycle

Höhfeld, J, Minami, Y, Hartl, FU

Cell 1995
18550409 Structure of the Hsp110:Hsc70 nucleotide exchange machine

Schuermann, JP, Jiang, J, Cuellar, J, Llorca, O, Wang, L, Gimenez, LE, Jin, S, Taylor, AB, Demeler, B, Morano, KA, Hart, PJ, Valpuesta, JM, Lafer, EM, Sousa, R

Mol. Cell 2008
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
adenyl-nucleotide exchange factor activity of HSP70 NEFs [cytosol]
Physical Entity
Activity
This event is regulated
Negatively by
Orthologous Events
Authored
Reviewed
Created